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Huangqin decoction alleviates lipid metabolism disorders and insulin resistance in nonalcoholic fatty liver disease by triggering Sirt1/NF-κB pathway

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World Journal of Gastroenterology 2023年第31期29卷 4744-4762页

作者： Bao-Fei Yan Lan-Fen Pan Yi-Fang Quan Qian Sha Jing-Zheng Zhang Yi-Feng Zhang Li-Bing Zhou Xi-Long Qian Xiao-Mei Gu Feng-Tao Li Ting Wang Jia Liu Xian Zheng College of Pharmacy Jiangsu Health Vocational CollegeNanjing 211800Jiangsu ProvinceChina Department of Pathology Affiliated Kunshan Hospital of Jiangsu UniversityKunshan 215300Jiangsu ProvinceChina Department of Education and Science The First People's Hospital of TaicangKunshan 215400Jiangsu ProvinceChina Department of Pharmacy Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221006Jiangsu ProvinceChina School of Pharmacy Nantong UniversityNantong 226019Jiangsu ProvinceChina Department of Pharmacy Affiliated Kunshan Hospital of Jiangsu UniversityKunshan 215300Jiangsu ProvinceChina School of Pharmacy Nanjing University of Chinese MedicineNanjing 210023Jiangsu ProvinceChina

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is a clinicopathological entity characterized by intrahepatic ectopic *** a consequence of increased consumption of high-calorie diet and adoption of a sedentary lifestyle,the incidence of NAFLD has surpassed that of viral hepatitis,making it the most common cause of chronic liver disease *** decoction(HQD),a Chinese medicinal formulation that has been used clinically for thousands of years,has beneficial outcomes in patients with liver diseases,including ***,the role and mechanism of action of HQD in lipid metabolism disorders and insulin resistance in NAFLD remain poorly *** To evaluate the ameliorative effects of HQD in NAFLD,with a focus on lipid metabolism and insulin resistance,and to elucidate the underlying mechanism of *** High-fat diet-induced NAFLD rats and palmitic acid(PA)-stimulated HepG2 cells were used to investigate the effects of HQD and identify its potential mechanism of *** in HQD were analyzed by highperformance liquid chromatography(HPLC)to identify the key *** Ten primary chemical components of HQD were identified by HPLC *** vivo,HQD effectively prevented rats from gaining body and liver weight,improved the liver index,ameliorated hepatic histological aberrations,decreased transaminase and lipid profile disorders,and reduced the levels of pro-inflammatory factors and insulin *** vitro studies revealed that HQD effectively alleviated PA-induced lipid accumulation,inflammation,and insulin resistance in HepG2 ***-depth investigation revealed that HQD triggers Sirt1/NF-κB pathwaymodulated lipogenesis and inflammation,contributing to its beneficial actions,which was further corroborated by the addition of the Sirt1 antagonist EX-527 that compromised the favorable effects of *** In summary,our study confirmed that HQD mitigates lipid metabolism disorders and insulin resistance i

关键词： Nonalcoholic fatty liver disease Huangqin decoction lipid metabolism disorders Insulin resistance Sirt1/NF-κB pathway

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Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury

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World Journal of Gastroenterology 2024年第9期30卷 1189-1212页

作者： Jin-Lian Jiang Yi-Yang Zhou Wei-Wei Zhong Lin-Yan Luo Si-Ying Liu Xiao-Yu Xie Mao-Yuan Mu Zhi-Gang Jiang Yuan Xue Jian Zhang Yi-Huai He Department of Infectious Diseases Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina Department of Infectious Diseases Jingmen Central HospitalJingmen 448000Hubei ProvinceChina Department of Respiratory Medicine Anshun People’s HospitalAnshun 561099Guizhou ProvinceChina Department of General Practice Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina Department of Intervention Radiology Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina School of Public Health Zunyi Medical UniversityZunyi 563099Guizhou ProvinceChina Department of Liver Diseases Third People’s Hospital of ChangzhouChangzhou 213000Jiangsu ProvinceChina Department of Digestion Dafang County People’s HospitalBijie 551600Guizhou ProvinceChina

BACKGROUND Uridine diphosphate glucuronosyltransferase 1A1(UGT1A1)plays a crucial role in metabolizing and detoxifying endogenous and exogenous ***,its contribution to the progression of liver damage remains *** To determine the role and mechanism of UGT1A1 in liver damage *** We investigated the relationship between UGT1A1 expression and liver injury through clinical ***,the impact and mechanism of UGT1A1 on the progression of liver injury was analyzed through a mouse model *** Patients with UGT1A1 gene mutations showed varying degrees of liver damage,while patients with acute-onchronic liver failure(ACLF)exhibited relatively reduced levels of UGT1A1 protein in the liver as compared to patients with chronic *** suggests that low UGT1A1 levels may be associated with the progression of liver *** mouse models of liver injury induced by carbon tetrachloride(CCl_(4))and concanavalin A(ConA),the hepatic levels of UGT1A1 protein were found to be *** mice with lipopolysaccharide or liver steatosis-mediated liver-injury progression,the hepatic protein levels of UGT1A1 were decreased,which is consistent with the observations in patients with ***1A1 knockout exacerbated CCl_(4)-and ConA-induced liver injury,hepatocyte apoptosis and necroptosis in mice,intensified hepatocyte endoplasmic reticulum(ER)stress and oxidative stress,and disrupted lipid *** UGT1A1 is upregulated as a compensatory response during liver injury,and interference with this upregulation process may worsen liver ***1A1 reduces ER stress,oxidative stress,and lipid metabolism disorder,thereby mitigating hepatocyte apoptosis and necroptosis.

关键词： Uridine diphosphate glucuronosyltransferase 1A1 Liver injury progression Endoplasmic reticulum stress Oxidative stress lipid metabolism disorders

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Targeting uridine diphosphate glucuronosyltransferase 1A1 in liver disease:Current research and future directions

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World Journal of Gastroenterology 2024年第39期30卷 4305-4307页

作者： Seok-Chan Park Yu Ji Kim Jong-Won Kim Department of Microbiology Icahn School of Medicine at Mount SinaiNew YorkNY 10029United States Division of Endocrinology and metabolism Department of Internal MedicineMedical SchoolJeonbuk National UniversityResearch Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University HospitalJeonju 54907South Korea Center for Pharmacogenetics and Department of Pharmaceutical Sciences University of PittsburghPittsburghPA 15216United States

The current letter to the editor pertains to the manuscript entitled'Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury'.Increased levels of uridine diphosphate glucuronosyltransferase 1A1 during liver injury could mitigate damage by reducing endoplasmic reticulum stress,oxidative stress,and dysregulated lipid metabolism,impeding hepatocyte apoptosis and necroptosis.

关键词： Uridine diphosphate glucuronosyltransferase 1A1 Liver injury Endoplasmic reticulum stress Oxidative stress lipid metabolism disorders

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Multi-omics: Opportunities for research on mechanism of type 2 diabetes mellitus

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World Journal of Diabetes 2021年第7期12卷 1070-1080页

作者： Shuai Wang Hui Yong Xiao-Dong He Institute of Toxicology School of Public HealthCheeloo College of MedicineShandong UniversityJinan 250012Shandong ProvinceChina Department of Physical and Chemical Inspection School of Public HealthCheeloo College of MedicineShandong UniversityJinan 250012Shandong ProvinceChina

Type 2 diabetes mellitus(T2DM)is a burdensome global ***-depth understanding of its mechanism will help to optimize diagnosis and treatment,which reduces the ***-omics research has unparalleled advantages in contributing to the overall understanding of the mechanism of this chronic metabolic *** the past two decades,the study of multi-omics on T2DMrelated intestinal flora perturbation and plasma dyslipidemia has shown tremendous potential and is expected to achieve major *** regulation of intestinal flora in diabetic patients has been confirmed by multiple *** use of metagenomics,16S RNA sequencing,and metabolomics has comprehensively identified the overall changes in the intestinal flora and the metabolic disturbances that could directly or indirectly participate in the intestinal flora-host *** combined with other“omics”has characterized lipid metabolism disorders in *** combined application and crossvalidation of multi-omics can screen for dysregulation in T2DM,which will provide immense opportunities to understand the mechanisms behind T2DM.

关键词： Type 2 diabetes mellitus Gastrointestinal microbiome Intestinal flora lipid metabolism disorders Dyslipidemias Metabolomics

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